Clock Genes: Critical Modulators of Breast Cancer Risk
Final rept. 2 Aug 2004-1 Aug 2005
ADELAIDE UNIV (AUSTRALIA)
Pagination or Media Count:
There is increasing evidence that disruption of circadian rhythms contributes to cancer. Circadian rhythms are regulated by a panel of specific transcription factors, called clock genes, and our current understanding of endogenous cellular rhythmicity is that both positive and negative feedback cycles of clock genes drive the expression of a growing list of other transcription factors and functional genes. It is possible that disruption of circadian control systems, which maintain normal cell function, could lead to malignant transformation into cancer cells. This concept is supported by recent findings that tumors grow faster in mice rendered arrhythmic by destruction of the suprachiasmatic nucleus, the bodys circadian clock. Furthermore, mice carrying a mutation in one of the core clock genes, per2, have disrupted circadian rhythmicity and are cancer prone, possibly due to permanent up-regulation of clock-controlled oncogenes. Rationale Epidemiological studies have linked shiftwork with an increased risk of breast cancer in humans, suggesting that circadian disruption may influence the development or progression of the disease. Previous studies, including our own have demonstrated rhythmicity of expression of key clock genes in mouse liver, heart, kidney, duodenum, ovary, lung and vascular tissue. As the patterns of expression were highly tissue-specific, it is critical to determine which clock and clock-controlled genes are expressed in mammary tissue and potentially contribute to the increased risk of breast cancer associated with shift work.
- Anatomy and Physiology
- Medicine and Medical Research